UBC Theses and Dissertations
Novel catalysis, photocaging, and positron emission tomography through bioconjugate chemistry Ting, Richard
This thesis is comprised of three projects that serve to address current topics in the field of bioorganic chemistry. Chapter 1 describes the emulation of enzyme catalysis through the kinetic analysis of the DNAzyme 9₂₅-11t, a combinatorially selected RNase A mimic utilizing imiclazole and amine groups hybridized to DNA. The rate constants measured for this system are the largest to date for M²⁺ -independent self cleavage (0.020 min⁻¹), trans cleavage (0.28 ± 0.02 min⁻¹), and multiple turnover (0.030 ± 0.002 min⁻¹) by a biomimetic system at physiological ionic strength and pH. These constants rival most combinatorially selected metal dependent DNAzymes and naturally occurring ribozymes even at physiological concentrations of M²⁺. Chapters 2 and 3 discuss a novel photochemical motif, its application to biologically relevant molecules, characterization of the photochemical mechanism, and its utility in the generation of alkenes. Light is considered superior to other chemical reagents as its spatial and temporal properties can be precisely controlled and its penetrative ability makes it a perfect reagent for the non- invasive perturbation of cellular processes. Chapter 2 details the discovery of a novel photochemical reaction and its use in photochemically regulating gene function and nucleic acid chemistry. The chemistry described in Chapter 2 holds potential for the photocaging of all adenine substrates, cofactors, and products in biological systems. Chapter 3 identifies the photolytic mechanism and highlights its application to photolytic alkene synthesis. It is predicted that the photolytic thioether mechanism identified in this chapter can be extrapolated to the photolysis of a wide range of other aromatic thioethers. Chapter 4 discusses the application of the ¹⁸F acceptor, boron, to most sensitive of in vivo molecular imaging techniques: positron emission tomography. This aqueous approach simplifies the state of the art by multiple chemical steps and multiplies the final specific radioactivity of the final radiotracer by a factor of 3. This tool is expected to widen the currently limited scope of biomarkers available for in vivo imaging and will enhance our ability to image biochemical targets and pathways such that insight may be gained in the progression, diagnosis, and treatment of disease.
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